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Using innovative imaging of 3D-engineered muscle to help develop new treatments for muscle wasting diseases

Dr Davina Simoes

University of Northumbria

The impact of muscle wasting

Sarcopenia is a muscle wasting condition affecting nearly a third of elderly people. It’s a natural part of the aging process but can lead to frailty, disability and early death. It can also have a significant impact on patients and their families, due to dependency and long hospital stays.

Sarcopenia can also develop in chronic conditions such as chronic lung or heart diseases and rheumatoid arthritis. However, not everyone with a chronic condition suffers from muscle wasting, so its underlying causes aren’t fully understood. Improved ways to understand and treat the condition are urgently needed.

With funding from Animal Free Research UK, Dr Davina Simoes, at the University of Northumbria, has developed an animal-free 3D muscle organoid, known as a ‘myooid’ (a mini version of a muscle) to study how human muscle cells grow and develop in people. Click here to read more >>

ChipCytometry – an innovative technique to study cells within muscle tissue

Microfluidic chips used in ChipCytometrty

Dr Simoes is now building on her pilot study research and has embarked on a partnership between The University of Northumbria, Animal Free Research UK, and ‘Canopy Biosciences’, a private ChipCytometry technology enterprise. ChipCytometry combines high-quality imaging with advanced image analysis software to create an accurate picture of how ‘biomarkers’ such as proteins, and molecules, are organised within a tissue. These biomarkers act like unique signposts within cells.

A key advantage of this technique is that it can measure multiple biomarkers at once. A tool called ‘immune profiling’ is used, whereby multiple antibodies are used to specifically match up with a biomarker. The antibodies are easily visualised using imaging machines as they are tagged with fluorescent molecules.

ChipCytometry is currently well established for measuring biomarkers for inflammation but has not been used to measure biomarkers for muscle growth. Part of this project will therefore involve optimising the technique so that for the first time, it can be used to pinpoint and measure biomarkers that are important in sarcopenia. Another advantage of ChipCytometry is that it can show how biomarkers are positioned in the three dimensional space of the cells, relative to one another.

Using a humanised ‘mini-muscle’ to understand muscle wasting

ChipCytometry image anlaysis software enabling the visualisation of different biomarkers using different fluorescently-tagged antibodies which attach to them

Dr Simoes aims to utilise ChipCytometry to shed light on how cells and molecules interact within the human 3D-sarcopenic muscle organoid, and precisely map how muscle growth is controlled.  She will focus on exploring the role of the complex 3D scaffold, known as the extracellular matrix. Dr Simoes is trying to determine if some of its components, in fact drive sarcopenia.

Sarcopenic and non-sarcopenic 3D-engineered human muscle samples from Dr Simoes’ lab will be loaded onto microfluidic chips (plastic chips with tiny fluid-filled channels) for analysis. Canopy Biosciences will carry out the biomarker imaging on both samples. When the imaging is complete, Dr Simoes will carry out follow-up analysis of the images in her lab.

The antibodies already validated for ChipCytometry are produced in animals or usually dissolved in bovine serum albumin (which comes from blood harvested from cattle at slaughter). In this project , five animal-free antibodies dissolved in animal-free solutions will be tested . This could provide new evidence that fully animal-free antibodies can be effectively used for ChipCytometry, paving the way for many more animal-free experiments using this technology.

Impact of this research

A deeper understanding of the role of particular molecules within muscle cells in sarcopenia could enable researchers to work towards a more personalised and therefore effective approach to developing treatments for people.

Longer term goals

As Canopy Biosciences has partnerships with leading labs in Universities across the globe, this project will facilitate collaborations beyond the UK that will help to advance knowledge of sarcopenia using ChipCytometry.

Animal-derived biomaterials are so embedded in current research, that only the development of cutting-edge animal-free technology can pave the way to an animal-free research culture.

The collaboration between Dr Simoes and Canopy Biosciences supports the strategy of Animal Free Research UK to advance animal-free technology. The project will act as proof of concept and will build towards the overarching goal of replacing the use of animals in biomedical research and testing, with non-animal human-relevant based methods and technologies.